Work on this project is designed to explain initial differences observed in various biophysical properties between membranes obtained from normal fibroblasts and those derived from individuals afflicted with Down's Syndrome (trisomy-21). Our studies consist of a careful exploration of two closely interlocking biochemical parameters, fluorescence characterization and molecular composition. Techniques have been and are continuing to be developed which utilize fluorescent membrane probes with the proper attendant spectroscopic technology which can be used to differentiate between normal and afflicted cell types. Since fluorescent measurements of this type have been equated with various functional membrane characteristics, we believe that valuable information can be obtained by relating the compositional aspects of membranes at the molecular level with observed functional membrane parameters. Consequently, we are in the process of developing analytical techniques designed to correlate changes observed in the fatty acid side chains of plasma membrane phospholipids derived from individuals of both classes utilizing capillary GC/MS techniques with biophysical changes as noted using fluorescent spectroscopy. Cell membrane characteristics of this nature will be further delineated by analysis of the results derived from "dilution jump" experiments, changes in surface receptor mobility, as well as a number of additional measurements, all of which are designed to exemplify differences between normal and abnormal membrane structure.